This is the fifth recompetition of the Massey Cancer Center (MCC) CCSG which has been continuously funded since 1975. Prior to the last review in 1990, there was substantial recruitment of new faculty to MCV/VCU and MCC with the creation of new programs shared resources. These new faculty have been integrated into collaborative cancer center activities with the development of projects highly relevant to the MCC mission. Faculty recruitment to MCC along with other achievements resulted in the creation of a Developmental Therapeutics Program with preclinical and clinical components. The preclinical component has strengths in new generation antimetabolites and dinuclear platinum compounds, DNA damage/repair, and biochemical and growth factor modulations. Clinical extrapolations of preclinical studies are planned on newly developed platinum agents, antifolates, and radiosensitizers. The further coalescence of molecular geneticists with MCC cellular and molecular biologists has resulted in important collaborative initiatives which have led to the further evolution of the programmatic structure of the center. All new shared resources approved in the last application, i.e., the Nucleic Acid Synthesis and Analysis, Molecular Biology, Structural Molecular Biology, Tissue Acquisition, and the Bone Marrow Transplantation Laboratories have grown and stimulated new interdisciplinary projects. In particular, the Bone Marrow Transplantation Shared Resource has spawned a constellation of research activities which have strong translational potential. Studies from the Structural Molecular Biology Shared Resource have resulted in a spectrum of collaborative research activities that have focused computational chemistry and structural biology concepts and technologies on cancer-relevant problems. There has been a substantial increase in clinical research activities with a doubling of available clinical protocols and a three-fold increase in investigator-initiated studies and patients entered into clinical trials since the last CCSG application. Cancer Control activities have achieved programmatic status and encompass (i) NIH-and ACS-supported chemoprevention trials, (ii) prevention initiatives based upon dissemination of information and technology to primary care physicians and, (iii) the development of a strong interdisciplinary health services research team that is now a national leader in the application of decision analysis and related technologies to assess outcomes and cost-effectiveness of cancer treatments. MCC has enhanced its position as a major regional cancer center. The MCC outreach program in rural Virginia is now well established in two sites and will extend to a third this spring, providing a network of advanced cancer care satellites for rural Virginians and a base for health services research. Associated prevention activities address the high mortality trends in these regions and studies have been initiated to assess the impact of this program on rural physician practice patterns, health care outcomes, and costs. Line item funding to the MCC from the Virginia legislature continues, and the addition of three floors to the MCC building received concept approval by the legislature and University approval for a capital construction/program development campaign. The MCC Citizen's Advisory Board has effectively enlisted community and political support for the center and its programs.